The spinocerebellar ataxias (SCAs) are a genetically and clinically heterogeneous group of neurodegenerative disorders. Relative frequencies vary within different ethnic groups and geographical locations.

1) To determine the frequencies of hereditary and sporadic adult onset SCAs in the Movement Disorders population; 2) to assess if the fragile X mental retardation gene 1 (FMR1) premutation is found in this population.

A retrospective chart review of individuals with a diagnosis of adult onset SCA was carried out. Testing for SCA types 1, 2, 3, 6, 7, and 8, Dentatorubral-pallidoluysian atrophy (DRPLA), Friedreich ataxia and the FMR1 expansion was performed.

A total of 69 patients in 60 families were identified. Twenty-one (35%) of the families displayed autosomal dominant and two (3.3%) showed autosomal recessive (AR) pattern of inheritance. A positive but undefined family history was noted in nine (15%). The disorder appeared sporadic in 26 patients (43.3%). In the AD families, the most common mutation was SCA3 (23.8%) followed by SCA2 (14.3%) and SCA6 (14.3%). The SCA1 and SCA8 were each identified in 4.8%. FA was found in a pseudodominant pedigree, and one autosomal recessive pedigree. One sporadic patient had a positive test (SCA3).Dentatorubral-pallidoluysian atrophy and FMR1 testing was negative.

A positive family history was present in 53.3% of our adult onset SCA patients. A specific genetic diagnosis could be given in 61.9% of dominant pedigrees with SCA3 being the most common mutation, followed by SCA2 and SCA6. The yield in sporadic cases was low. The fragile X premutation was not found to be responsible for SCA.

Recently, a single base pair substitution (G1747A) mutation of the neurofilament M (NF-M) gene was reported in a French-Canadian patient with early onset Parkinson’s disease (PD). Three unaffected siblings were found to be heterozygotes for the NF-M Gly336Ser mutation but, to date, no other affected PD individuals have been found with a similar mutation. No other individuals with Parkinson’s disease and of similar ethnic background have been screened for this mutation.

We screened 102 French-Canadian patients with definite PD and 45 French-Canadian controls for this substitution in the NF-M gene using a PCR-restriction enzyme digestion method.

None of the patients or controls carried this mutation.

Our results would indicate that this mutation is not common even in a PD population of similar ethnic background and suggest this change represents a rare variant. However, these results do not exclude the possibility that other mutations in this gene could be present.

Rett syndrome (RTT) is a severe neurodevelopmental disorder of girls, caused by mutations in the X-linked MECP2 gene. Worldwide recognition of the RTT clinical phenotype in the early 1980's allowed many cases to be diagnosed, and established RTT as one of the most common mental retardation syndromes in females. The years since then led to a refinement of the phenotype and the recent elaboration of Revised Diagnostic Criteria (RDC). Here, we study the impact of the presence versus the absence of the use of diagnostic criteria from the RDC to make a diagnosis of RTT on MECP2 mutation detection in Canadian patients diagnosed and suspected of having RTT.

Using dHPLC followed by sequencing in all exons of the MECP2 gene, we compared mutation detection in a historic cohort of 35 patients diagnosed with RTT without the use of specific diagnostic criteria to a separate more recent group of 101 patients included on the basis of strict fulfillment of the RDC.

The MECP2 mutation detection rate was much higher in subjects diagnosed using a strict adherence to the RDC (20% vs. 72%).

These results suggest that clinical diagnostic procedures significantly influence the rate of mutation detection in RTT, and more generally emphasize the importance of diagnostic tools in the assessment of neurobehavioral syndromes.

The aim of the present study was to assess visual alterations in a population of Argentine patients treated with the antiepileptic drug vigabatrin.

Twenty patients receiving vigabatrin and 15 patients receiving carbamazepine were examined with automated perimetry using a Humphrey 120-point full screening strategy. In addition, scotopic flash electroretinograms were performed.

Of 20 patients treated with vigabatrin, two were unable to cooperate with testing. Of the remaining 18 patients, all but two showed at least one non-detected point inside the central 40° of the visual field of each eye. Of the 15 carbamazepine-treated patients, three were unable to perform the study. None of the remaining 12 patients showed visual field defects. Both a- and b-wave amplitudes of the scotopic electroretinogram were significantly reduced in 12 patients receiving vigabatrin.

Visual field defects among patients on vigabatrin therapy may occur with a higher frequency than previously recognized. The Humphrey 120-points full field screening test and electroretinography are useful tools to assess the visual dysfunction associated with vigabatrin.

Changes in brain lesion loads assessed with magnetic resonance imaging obtained at 1.5 Telsa (T) are used as a measure of disease evolution in natural history studies and treatment trials of multiple sclerosis.

A comparison was made between the total lesion volume and individual lesions observed on 1.5 T images and on high-resolution 4 T images. Lesions were quantified using a computer-assisted segmentation tool.

There was a 46% increase in the total number of lesions detected with 4 T versus 1.5 T imaging (p<0.005). The 4 T also showed a 60% increase in total lesion volume when compared with the 1.5 T (p<0.005). In several instances, the 1.5 T scans showed individual lesions that coalesced into larger areas of abnormality in the 4 T scans. The relationship between individual lesion volumes was linear (slope 1.231) showing that the lesion volume observed at 4 T increased with the size of the lesion detected at 1.5 T. The 4 T voxels were less than one quarter the size of those used at 1.5 T and there were no consistent differences between their signal-to-noise ratios.

The increase in signal strength that accompanied the increase in field strength compensated for the loss in signal amplitude produced by the use of smaller voxels. This enabled the acquisition of images with improved resolution, resulting in increased lesion detection at 4 T and larger lesion volumes.

Carotid ultrasound (US) is a screening test for patients with transient ischemic attacks (TIAs) or stroke who then undergo Digital Subtraction Angiogram (DSA) or Magnetic Resonance Angiography (MRA). Gold standard DSA is invasive with inherent risks and costs. MRA is an evolving technology. This study compares reliability of MRA and US modes with DSA in determining degree of internal carotid artery stenosis.

A five year retrospective analysis of 140 carotid arteries from patients who had carotid US and DSA, and possibly Magnetic Resonance Angiography was undertaken. Recorded US parameters were peak systolic velocity (PSV), end diastolic velocity (EDV), and ICA/CCA peak systolic velocity ratio. The MRA and DSA parameters used NASCET technique for measuring stenosis. Statistical analysis included ROC curves and Kappa computation.

US grading of carotid stenosis can be made more reliable by choosing appropriate parameters. The best combination of sensitivity and specificity for stenosis > 70% in our hospital was seen at PSV > 173cm/s (sensitivity 0.87, specificity 0.8, Positive Predictive Value (PPV) 0.70, Negative Predictive Value (NPV) 0.93, kappa 0.64 and weighted kappa 0.71). MRA kappa was 0.78, (sensitivity 0.75, specificity 1.0, PPV 1.0, NPV 0.85).

US parameters should be validated in each centre. At best, US can only approximate the accuracy of DSA, probably due to inherent limitations of this modality. Magnetic Resonance Angiography has a perfect specificity and PPV but this technique needs to be standardized. Simultaneous use of MRA and US for screening increases sensitivity to over 0.9 without compromising specificity in > 70% stenosis.

Pulmonary and respiratory muscle function impairment are common in patients with Parkinson's disease (PD). Inspiratory muscle training may improve strength, dyspnea and functional capacity in healthy subjects and in those with chronic obstructive pulmonary disease. This study investigated the effect of specific inspiratory muscle training (SIMT) on pulmonary functions, inspiratory muscle performance, dyspnea and quality of life, in patients with PD.

Twenty patients with PD (stage II and III Hoehn and Yahr scale) were recruited for the study and were divided into two groups: a) ten patients who received SIMT and b) ten patients who received sham training, for three months. Pulmonary functions, the respiratory muscle strength and endurance, the perception of dyspnea (POD) and the quality of life were studied before and within one week after the training period. All subjects trained daily, six times a week, each session consisting of 1/2 hour, for 12 weeks.

Following the training period, there was a significant improvement, in the training group but not in the control group, in the following parameters: inspiratory muscle strength, (PImax, increased from 62.0±8.2 to 78.0±7.5 cm of H2O (p<0.05), inspiratory muscle endurance (increased from 20.0±2.8 to 29.0±3.0 cm of H2O (p<0.05), and the POD (decreased from 17.9±3.2 to 14.0±2.4 units (p<0.05). There was a close correlation between the increase in the inspiratory muscle performance and the decrease in the POD.

The inspiratory muscle performance may be improved by SIMT in patients with PD. This improvement is associated with a significant decrease in their POD.

To describe the results, technical feasibility, efficacy and challenges encountered in our preliminary experience using a self-expandable microstent, optimized for intracranial use, as an adjunct in the endovascular treatment of wide-necked aneurysms.

Only broad-necked aneurysms (dome-to-neck ratio £2, or an isolated neck size > 4.5 mm) were treated with Neuroform microstent from July 2003 to May 2004. The techniques used for stent deployment were either parallel or sequential. Angiographic results were recorded immediately for all patients and classified as Class 1 (complete occlusion), Class 2 (neck remnant) or Class 3 (sac remnant) by three interventional neuroradiologists not involved in the procedure. Follow-up angiography at six months was obtained for one case. Modified Rankin Score scale was assessed for all patients.

Seventeen intracranial aneurysms in a total of 18 patients were treated (mean age, 52.2 yr). Eight patients (44.4%) presented with acute subarachnoid hemorrhage. Eleven aneurysms (61.1%) were in the posterior circulation. Average dome size was 10.2 mm (range, 3.7-19.8 mm) and average neck size was 5.36 mm (range, 3.0-10.0 mm). Six out of seven aneurysms of the anterior circulation were approached with parallel technique. Eight aneurysms of the posterior circulation were approached with sequential technique. Average number of coils deployed was 9.64 (range, 4-23 coils). Eleven aneurysms (64.8%) resulted in Class 1 and/or Class 2. One technical failure was observed. Technical complications were recognized in four patients (23.5%), all of them with unruptured aneurysms in the anterior circulation. Two patients (11.7%) presented transient immediate clinical complications. One patient (5.8%) had minor permanent neurological complication. Neither major clinical complications nor death were encountered. Favorable clinical outcome (Modified Rankin Scale score 0-2) was observed in 88.2% of the patients (average follow-up time, 4.72 months).

Absence of major permanent complications and satisfactory immediate obliteration degree in our preliminary experience indicates that microstent-assisted coiling technique is useful for the minimally invasive treatment of broad-necked complex aneurysms that are not ideal for conventional endovascular treatment and are at a high risk for conventional surgical treatment.

Doppler ultrasound (DUS) is used as a screening tool to assess internal carotid artery (ICA) disease. Recent reports suggest that the DUS may be inaccurate in over 28% of patients. We sought to evaluate the accuracy of DUS, when performed in a dedicated stroke prevention clinic (SPC).

We retrospectively reviewed the charts of patients who had a DUS performed in our SPC, followed by conventional cerebral angiography. Three groups of patients were defined. Group 1 had DUS measured ICA stenosis of >50%; Group II had a DUS measured ICA stenosis of <50%; Group III had complete ICA occlusion on DUS.

Sixty-seven patients (69 arteries) were included in the study. There were 45 patients in Group I and based on the findings of cerebral angiography, carotid endarterectomy was considered inappropriate in only one patient. - a misclassification rate of 2.2% (95%CI: 0 – 6.5%). Group II consisted of 19 patients and on cerebral angiography, none of these patients had a stenosis of >50% - a misclassification rate of 0%. Group III consisted of five patients in whom DUS showed complete ICA occlusion. The angiogram confirmed the occlusion in all five patients – a misclassification rate of 0%. Overall, misclassification rate was 1.45% (95% CI: 0 - 4.3%).

Doppler ultrasound when performed in a stroke prevention clinic (SPC), has a high accuracy in measuring ICA stenosis of >50%. Doppler ultrasound is reliable in detecting complete ICA occlusion and finally DUS is a reliable screening tool to rule out clinically significant ICA stenosis.

To determine the impact of check size and interstimulus interval (ISI) on neuromagnetic visual cortical responses.

We recorded visual evoked fields to pattern-reversal stimulation with central occlusion in ten subjects. The ~100 ms magnetic activation (P100m) was analyzed by single dipole modeling.

With 1 s ISI, P100m strengths increased as check size increased from 15' up to 120' of visual arc, and larger checks elicited less P100m activation. With 120' checks, we found no P100m attenuation as ISI decreased from 4 s to 0.16 s. P100m sources around the calcarine sulcus did not vary with check size or ISI.

The magnitude of cortical activation during visual contrast processing is check size-dependent and the 120' checks are optimum for future studies on neuromagnetic visual cortical functions using central-occluded stimulation. The corresponding neuronal activation demonstrated a short refractory period less than 0.16 s. We also found significantly overlapping cortical representation areas for different check sizes or ISIs.

Impaired gastrointestinal motility in Parkinson’s disease may affect absorption of levodopa and contribute to the disabling response fluctuations (RF). In this study gastric myoelectric activity was recorded with electrogastrography in patients with PD and correlated with the duration, severity and the presence of RF.

Electrogastrography (EGG) was performed in 36 patients with PD of which 22 were men. The mean age was 67 years (48-81), mean duration of disease was 7.07 years (1-20), and mean duration of treatment with levodopa was 5.07 years (1-20). Gastric dysrrythmia was diagnosed when either preprandial or postprandial dysrrythmia for more than 30% of the recording period was detected.

The EGG was abnormal in 24 of 36 patients. Significant association was found between preprandial dysrrythmia and duration of disease (P=0.002); duration of levodopa treatment (P=0.003), severity of 86RF (P=0.001), but not with age (P=0.076). Out of 18 patients with RF, 17 had at least one pattern of dysrrythmia. In 11 out of the 18 patients without RF, the EGG was normal while the remaining seven had at least one pattern of dysrrythmia.

Abnormal EGG was quite common in this group of patients with PD, particularly in those with RF. The most common pattern of abnormality was preprandial dysrrythmia, which was positively associated with disease duration and length of levodopa treatment. Although frequently asymptomatic, preprandial dysrrythmia leading to impaired gastric emptying may contribute to irregular absorption of levodopa from the small intestine and contribute to disabling response fluctuations.

To report the residency training experience of two neurologists, focusing on setting and diagnoses encountered.

Data from prospective patient logs kept by the authors during residencies completed a decade apart were compared with each other and the literature.

The range of diagnoses was broadly similar between residencies, as were the proportions of common or uncommon disorders, and the proportion of cases without a neurological diagnosis. Although most patients were seen in in-patient settings, the rates at which common neurological conditions and functional disorders were seen was comparable to published experiences of community neurologists.

The diagnostic profile of North American neurology residency appears to be relatively stable, regardless of location or date of training. In several respects, the content of current neurology residencies mirrors clinical practice well. Changes to residency training are doubtless needed, but they should be guided by a clear understanding of the experiences of contemporary trainees.

To determine physical and cognitive outcomes of full-term infants who suffered intracranial hemorrhage (ICH) at birth.

A retrospective hospital-based, follow-up study of infants treated in London, Ontario between 1985 and 1996. Follow-up was conducted by telephone interviews and clinic visits. Outcome was measured according to physical and cognitive scales. Perinatal risk factors and hemorrhage characteristics were correlated with final outcome.

For this study 66 infants with ICH were identified, of which seven died during the first week of life. We obtained follow-up in all but ten cases (median = 3-years; range 1.0 to 10.9 years). Overall, 57% of infants had no physical or cognitive deficits at follow-up. Death occurred most frequently among those with primarily subarachnoid hemorrhage (19%) and the most favorable outcomes occurred among those with subdural hemorrhage (80% had no disability). In univariate models, thrombocytopenia (platelet count ≤ 70 x 109/L), increasing overall hemorrhage severity, frontal location and spontaneous vaginal delivery as opposed to forceps-assisted delivery increased risk for poor outcome. In multivariate models, all these factors tended towards increased risk, but only thrombocytopenia remained significant for physical disability (OR = 7.6; 95% CI = 1.02 – 56.6); thrombocytopenia was borderline significant in similar models for cognitive disability (OR = 4.6; 95% CI = 0.9 – 23.9).

Although forceps-assisted delivery may contribute to ICH occurrence, our study found better outcomes among these infants than those who had ICH following a spontaneous vaginal delivery. Hemorrhage in the frontal lobe was the most disabling hemorrhage location and if multiple compartments were involved, disability was also more likely to occur. However, in this report we found that the factor that was most likely to contribute to poor outcome was thrombocytopenia and this remained important in multivariate analysis.

To date, few pediatric series of neurofibromatosis type 1 (NF-1) have been described in the literature even though it is the most frequently encountered phakomatosis.

We reviewed 987 charts of pediatric patients with a presumptive diagnosis of NF-1 who were evaluated at Ste-Justine hospital from January 1, 1991 to July 31, 2002. Patients who presented with two or more cardinal criteria were diagnosed with NF-1. Clinical and laboratory data were retrospectively collected, including: demographics, neuroimaging and presence or absence of associated symptoms or signs of NF-1.

A total of 279 patients were diagnosed with NF-1. The mean age at diagnosis was 3.4 years. Ninety-nine percent of the patients had café au lait spots and 47% had a first degree relative with NF-1. Almost 60 percent (59.6%) of those seen by an ophthalmologist had Lisch nodules. Optic glioma was found in in 14.7%, cutaneous neurofibromas in 38.4%, plexiform neurofibromas in 24.7%, neurofibrosarcoma in 1.8%, learning disabilities in 39%, attention deficit disorder in 40.5%, osseous dysplasias in 7.2%, pseudoarthrosis in 3.6%, precocious puberty in 3.2% and short stature in 17.9%. Magnetic resonance, when performed, showed hyperintense T2 lesions in 87.1% of cases. The mean period of follow-up was 7.4 years.

Neurofibromatosis type 1 is a multisystemic disorder associated with increased risk of malignancy. It can be diagnosed at a very young age and clinical follow-up is advised. To our knowledge, this is the largest single center study of NF-1 in a pediatric population.

Although severe traumatic brain injury (sTBI) is a devastating condition with tremendous public health implications, the epidemiology of this disease has not previously been described in Canada. We sought to define the incidence, risk factors and outcome of patients suffering sTBI in a large Canadian region.

A population-based surveillance cohort design was utilized to identify all Calgary Heath Region residents who were victims of trauma with an injury severity score ³12. Subsequent application of a specific sTBI case definition defined the final cohort.

The annual incidence of sTBI was 11.4 per 100,000 population. The incidence of sTBI was significantly higher for males as compared to females [17.1 vs. 5.9 per 100,000; relative risk (RR) = 2.91, 95% confidence interval; 2.17, 3.94; p<0.0001]. There was a striking increase in the annual age specific population incidence of sTBI observed among those older than 74 years of age. The relative risk among the highest risk group of elderly (>85 years) males as compared to the lowest risk female group (50-64 years) was 19.78 (95% CI; 6.27, 62.3; p<0.0001). One hundred and eight patients died prior to hospital discharge for a mortality rate of 5.1 per 100,000 per year.

Severe traumatic brain injury is common among residents of the Calgary Health Region and is associated with a high mortality rate. Males and the elderly are at the highest risk for acquiring sTBI and may represent target groups for preventive efforts.

Les lÉsions cÉrÉbrales par traumatisme crânien sÉvère sont frÉquentes parmi les rÉsidents de la rÉgion sanitaire de Calgary et sont associÉes à une mortalitÉ ÉlevÉe. Les hommes et les personnes âgÉes sont les groupes les plus à risque et constituent des groupes cibles pour les interventions à visÉe prÉventive.

Focal cortical dysplasia (FCD) is one of the most common underlying pathologic substrates in patients with medically intractable epilepsy. While magnetic resonance imaging (MRI) evidence of FCD is an important predictor of good surgical outcome, conventional MRI is not sensitive enough to detect all lesions. Previous reports of diffusion tensor imaging (DTI) abnormalities in FCD suggest the potential of DTI in the detection of FCD. The purpose of this study was to study subcortical white matter underlying small lesions of FCD using DTI.

Five patients with medically intractable epilepsy and FCD were investigated. Diffusion tensor imaging images were acquired (20 contiguous 3mm thick axial slices) with maps of fractional anisotropy (FA), trace apparent diffusion coefficient (trace/3 ADC), and principal eigenvalues (ADC parallel and ADC perpendicular to white matter tracts) being calculated for each slice. Region of interest analysis was used to compare subcortical white matter ipsilateral and contralateral to the lesion.

Three subjects with FCD associated with underlying white matter hyperintensities on T2 weighted MRI were observed to have increased trace/3 ADC, reduced fractional anisotropy and increased perpendicular water diffusivity which was greater than the relative increase in the parallel diffusivity. No DTI abnormalities were identified in two patients with FCD without white matter hyperintensities on conventional T2-weighted MRI.

While DTI abnormalities in FCD with obvious white matter involvement are consistent with micro-structural degradation of the underlying subcortical white matter, DTI changes were not identified in FCD lesions with normal appearing white matter.

To evaluate the role of methadone in the management of intractable neuropathic noncancer pain.

A case series of 50 consecutive noncancer pain patients who were seen at a tertiary care centre and treated with oral methadone for a variety of intractable neuropathic pain states.

The mean age was 52.7 years and the mean duration of follow-up was 13.9 months. Post-discectomy nerve root fibrosis, complex regional pain syndrome, peripheral neuropathy and central spinal cord pain syndromes were the most common diagnoses. Over 90% had been treated with one or more tricyclic antidepressants and anticonvulsants and a similar number had received other adjuvant analgesics. All patients had failed treatment with one or more conventional opioid analgesics (mean 2.8) at a mean maximal morphine dose of 384 mg (or equivalents) per day. Twelve patients had failed spinal cord stimulation. Nineteen patients (38%) did not tolerate initial methadone titration or thought their pain was worse on methadone. Five patients (10%) declared initial benefit but required repetitive dose escalation and eventually became non-responders. Twenty-six patients (52%) reported mild (4), moderate (15), marked (6) or complete (1) pain relief and continued on methadone at a mean maintenance dose of 159.8 mg/day for a mean duration of 21.3 months. Fourteen patients (28%) reported improved function on methadone relative to previous treatments.

Methadone appears to have unique properties including N-methyl-D-aspartate antagonist activity that may make it especially useful in the management of intractable neuropathic pain. This observation needs to be tested in randomized, controlled trials.

To determine the mean time for acquiring computed tomogram perfusion (CTP) and CT angiogram (CTA) images in acute stroke. To determine and compare processing and interpretation times amongst three groups of radiologists with varying degree of expertise: two radiology residents (Group I), two neuroradiology fellows (Group II) and four consultant neuroradiologists (Group III).

The mean time of acquisition of CTA and CTP studies was calculated among ten patients presenting with acute stroke. All readers had to process the CTA and CTP images, interpret them (for presence or absence of thrombus and penumbra) and save them on the GE Advantage Windows workstation. The mean time for processing and interpreting these studies was calculated.

The mean time for acquisition of CTA and CTP studies in the ten patients was 14.6 ± 5.9 minutes. The time taken for CTA processing and interpretation in Groups I, II and III was 2.3 ± 1.3 min, 1.6 ± 0.4 min and 1.5 ± 0.7 min respectively. The time required for CTP processing and interpretation by the same groups was 5.2 ± 1.7 min, 4.5 ± 1.5 min and 4.1 ± 1.1 min respectively. There was a statistically significant difference of means between Groups I and III in the CTA and CTP processing and interpretation times (p=0.02, p=0.01 respectively) but no statistical difference between Groups I and II (p=0.15, p=0.22 respectively) or Groups II and III (p=0.31, p=0.30 respectively).

The CTA and CTP studies can be performed, processed and interpreted quickly in acute stroke.

Clobazam is a benzodiazepine with known antiepileptic action; however, it is not considered first line therapy in the treatment of epilepsy. The objective of this study was to evaluate the efficacy of clobazam as add-on therapy in adults with temporal lobe epilepsy associated with MRI evidence of hippocampal sclerosis (HS).

This is a retrospective study, conducted at our epilepsy clinic which evaluated clobazam as add-on therapy in patients with temporal lobe epilepsy and MRI signs of HS. Clobazam was prescribed based on the minimum effective dose up to the maximum tolerated dose.

Seventy-eight patients met the inclusion criteria (51 women), ages ranging from 16 to 76 years old (mean=42.2). Dosage of clobazam ranged from 5 to 60 mg/day (mean=22.6 mg/day). Clobazam was used from one month to eight years (mean=29 months). Sixteen (20.5%) patients were seizure-free, 20 (25.5%) had more than 75% improvement in seizure control, eight (10%) had more than 50% and 20 (26%) were non responders to clobazam. In 14 (18%) we could not determine seizure frequency during follow-up. The improvement in seizure control lasted for more than one year in 30 (68%) patients.

Our data suggest that clobazam should be considered as add-on therapy in the treatment of patients with temporal lobe epilepsy associated with MRI signs of HS.

Controversial data was published about the sodium channel-blocking effect of the endogenous pentapeptide QYNAD, which is elevated in patients with multiple sclerosis and Guillain-Barré-syndrome. In some experiments with single cells and nerve preparations QYNAD inhibited sodium currents to the same extent as the known sodium channel blocker lidocaine whereas in other laboratory testing QYNAD failed to show any effect at all.

Micro-electrode arrays with cultured neuronal networks are highly suitable to determine neuroactive activity of applied substances. The impact on electrophysiological parameter changes was compared between QYNAD and the established sodium channel blockers lidocaine and tetrodotoxin (TTX).

QYNAD did not alter network activity whereas the sodium channel blockers lidocaine (IC50 14.9 µM) and tetrodotoxin (IC50 1.1 nM) reversibly decreased network activity in similar concentrations as in patch-clamp experiments. This decrease of spontaneous electrophysiological activity was achieved by prolonging the interburst-interval.

Although QYNAD might have mild effects on single-cell sodium currents, there is no significant effect on neuronal network function. These results raise concerns about QYNAD exhibiting a relevant impact on functional disability of the central nervous system in patients.